The goal of this Training Program is to provide graduate students with advanced education in fundamental aspects of macromolecular chemistry, structure and mechanism. The program focuses on the basic physical-chemical and structural principles that give biological macromolecules their huge versatility of action in the living cell. The Training Program provides support for graduate students enrolled in two graduate programs here: Biochemistry, a highly structured program drawing students mainly from chemistry backgrounds, and Biophysics & Structural Biology, a relatively unstructured program for students from diverse quantitative undergraduate backgrounds. These two graduate programs, currently training a total of 59 students, operate within a larger group of four graduate programs in the life sciences. This Training Program involves 20 participating faculty from four university departments and provides training in the following areas: protein and nucleic acid structure determination by x-ray crystallography, cryo-electron microscopy, and magnetic resonance, mechanistic enzymology, single-molecule tracking analysis, catalytic RNA mechanisms, membrane protein structure and function, and mechanistic investigations of numerous specialized systems. All graduate students take a program of rigorous, quantitative courses and advanced research seminars, and all carry out 4 laboratory rotations in the first year. Students choose Ph.D. thesis advisors at the end of the first academic year m and typically proceed to the Ph.D. degree over the next four years. An overarching rationale of this program is that human disease must ultimately be understood in terms of the chemistry and physics of biological macromolecules.